Background:Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased thromboembolic stroke risk and heart failure. Although various prediction models for AF risk have been developed using machine learning, their output cannot be accurately explained to doctors and patients. Therefore, we developed an explainable model with high interpretability and accuracy accounting for the non-linear effects of clinical characteristics on AF incidence.

Methods and Results:Of the 489,073 residents who underwent specific health checkups between 2009 and 2018 and were registered in the Kanazawa Medical Association database, data were used for 5,378 subjects with AF and 167,950 subjects with normal electrocardiogram readings. Forty-seven clinical parameters were combined using a generalized additive model algorithm. We validated the model and found that the area under the curve, sensitivity, and specificity were 0.964, 0.879, and 0.920, respectively. The 9 most important variables were the physical examination of arrhythmia, a medical history of coronary artery disease, age, hematocrit, γ-glutamyl transpeptidase, creatinine, hemoglobin, systolic blood pressure, and HbA1c. Further, non-linear relationships of clinical variables to the probability of AF diagnosis were visualized.

Conclusions:We established a novel AF risk explanation model with high interpretability and accuracy accounting for non-linear information obtained at general health checkups. This model contributes not only to more accurate AF risk prediction, but also to a greater understanding of the effects of each characteristic.

Background:Patients with heart failure (HF) often experience gastrointestinal problems such as constipation, diarrhea, and disturbances to drug absorption. In HF, hypoperfusion and congestion cause structural and functional changes in the gut, which, in turn, lead to impaired cardiac function.Euglena gracilisZ (hereafter “Euglena”), calledMidorimushiin Japanese, is a microalga that is used as a food or nutritional supplement. It is unclear whether Euglena is beneficial for bowel habitus and cardiac function in subjects with HF.

Methods and Results:We injected C57BL/6 male mice subcutaneously with isoproterenol (ISO) (20 mg/kg/day) for 7 days to examine bowel movement in HF. Euglena was orally administered to mice on anad libitum-feeding to a normal chow containing 2% dietary mixture. ISO induced a decrease in bowel movement and an increase in fecal retention in the cecum, as well as a decrease in left ventricular (LV) contraction. Euglena accelerated intestinal transit, relieved fecal retention, and prevented the alterations in gut pathology in ISO-treated mice. Euglena also suppressed ISO-induced decreases in LV contraction, although it had no significant effect on LV hypertrophy.

Conclusions:The results suggested that oral administration of Euglena alleviated constipation and cardiac dysfunction in a mouse model of ISO-induced HF, and highlight the potential clinical benefit of Euglena in patients with HF in preventing constipation and contractile deterioration.

Background:The cardio-ankle vascular index (CAVI) is associated with the severity of vascular stiffness and heart failure (HF). However, little is known about CAVI in aortic stenosis (AS) patients, probably because of the difficulty of accurately measuring CAVI in these patients owing to their slow-rising pulse. In this study, we investigated the prevalence and prognostic impact of abnormally elevated CAVI measured after transcatheter aortic valve implantation (TAVI).

Methods and Results:Among patients with AS who underwent TAVI, those with bilateral peripheral artery disease, atrial fibrillation, and systolic HF were excluded. The effect of post-TAVI elevated CAVI (defined as ≥9.0) on HF readmission after the index discharge was investigated. In all, 149 patients (mean [±SD] age 84.8±5.6 years, 24.2% men, mean [±SD] post-TAVI CAVI 9.6±1.4) were included in the study. There was no significant difference in baseline characteristics between groups with and without elevated CAVI, except for lower high-density lipoprotein cholesterol (HDL-C) and a higher prevalence of HF history in the group with elevated CAVI (P<0.05 for both). Post-TAVI elevated CAVI (n=102) was associated with lower freedom from HF recurrence during the observational period (89.1% vs. 100%; median 726 days [interquartile range 329–1,104 days]; P<0.05). Moreover, CAVI was an independent predictor of HF occurrence (hazard ratio 1.62; 95% confidence interval 1.07–2.46; P=0.022).

Conclusions:Elevated CAVI was associated with HF occurrence before and after TAVI.

Background:The complication of left ventricular (LV) hypertrophy (LVH) is associated with increased incidence of major cardiovascular events. Hypertension is an independent risk factor among several factors contributing to the development of LVH, and thus appropriate treatment of both hypertension and LVH reduces the risk of developing heart failure. Mineralocorticoid-receptor blockers (MRBs) have been reported to improve the prognosis of LVH, but use of currently available MRBs is limited by adverse events. Esaxerenone is a novel selective nonsteroidal MRB recently approved for treatment of hypertension. Although the renoprotective effect of esaxerenone has been demonstrated in both preclinical and clinical studies, little data is available in terms of its cardioprotective effects.

Methods and Results:This multicenter, open-label, exploratory interventional study was designed to evaluate the safety and efficacy of esaxerenone in combination with renin-angiotensin system (RAS) inhibitors or calcium-channel blockers (CCBs). Eligible criteria are hypertensive patients with LVH, and target blood pressure (BP) not reached with an RAS inhibitor or a CCB. The primary endpoints are change from baseline in seated home BP (early morning systolic/diastolic BPs), and change and %change from baseline in the LV mass index at the end of treatment.

Conclusions:This study will provide the first clinical evidence of the antihypertensive effect and safety of esaxerenone in hypertensive patients with LVH.